Department of Periodontology, Nanjing Stomatological Hospital, Medical School of Nanjing University , Nanjing 210093, Jiangsu, P. R. China.
Department of Radiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing University , Nanjing 210008, Jiangsu, P. R. China.
ACS Appl Mater Interfaces. 2018 Jan 31;10(4):3405-3413. doi: 10.1021/acsami.7b17323. Epub 2018 Jan 18.
The combination of WO and tirapazamine (TPZ) core has been first introduced into the preparation of poly(ε-caprolactone)-poly(ethylene glycol) (PL) surrounded nanoparticles (NPs). The aim of using WO is employing its capability of reacting with the absorbed O to generate reactive oxygen species (ROS) when exposed to a long-wavelength laser at 808 nm to increase skin penetration and body tolerance. In this work, we have demonstrated that WO unit gives rise to more hypoxic tumor microenvironment and activates the prodrug TPZ to achieve hypoxia-activated chemotherapy, which could be monitored by the intracellular ROS/hypoxia detection and in vivo positron emission tomography imaging. In addition, the successful introduction of WO into PL-WO-TPZ NPs could render the photothermal therapy under the irradiation of an 808 nm laser. As a result, in vivo antitumor results have clearly shown that PL-WO-TPZ NPs could efficiently erase the solid tumor tissues by means of simultaneous hypoxia-activated chemotherapy and photothermal therapy. In comparison to the costly small-molecule photosensitizer chlorine e6 used in hypoxia-activated chemotherapy, WO NPs have two advantages of large-scale preparation and additional photothermal therapy effect, which could provide new insight into future clinical applications.
WO 和替拉扎胺（TPZ）核心的组合首次被引入聚（ε-己内酯）-聚（乙二醇）（PL）包围的纳米颗粒（NPs）的制备中。使用 WO 的目的是利用其在 808nm 长波长激光照射下与吸收的 O 反应生成活性氧物种（ROS）的能力，以增加皮肤穿透性和身体耐受性。在这项工作中，我们已经证明，WO 单元会导致缺氧肿瘤微环境，并激活前药 TPZ 以实现缺氧激活化疗，这可以通过细胞内 ROS/缺氧检测和体内正电子发射断层扫描成像来监测。此外，WO 成功地引入到 PL-WO-TPZ NPs 中可以在 808nm 激光照射下进行光热治疗。结果，体内抗肿瘤结果清楚地表明，PL-WO-TPZ NPs 可以通过同时进行缺氧激活化疗和光热治疗有效地消除实体肿瘤组织。与用于缺氧激活化疗的昂贵小分子光敏剂氯 e6 相比，WO NPs 具有大规模制备和额外光热治疗效果的两个优势，这可为未来的临床应用提供新的见解。
